The Serbian SuperLiga champions have lost one and drawn one of their opening two matches.
Match preview
Leipzig, meanwhile, have performed largely to expectations by beating Young Boys 3-1 in their opening game, before being defeated by the same scoreline by the holders Manchester City at the Red Bull Arena.
Die Roten Bullen were close to gaining a point against Pep Guardiola's side when Lois Openda cancelled out Phil Foden's opener, but late goals from Julian Alvarez and Jeremy Doku secured all three points for the visitors.
Domestically, Marco Rose's side returned to winning ways with a 3-1 victory against SV Darmstadt 98 on Saturday, having frustratingly dropped two points in a 0-0 draw at home against VfL Bochum prior to the international break.
That win moved Leipzig up to fifth place in the Bundesliga - five points behind league leaders Bayer Leverkusen - suggesting that they remain on course to achieve their primary objective of qualifying for the Champions League once again.
Rose and his players will also have ambitions of lifting the DFB-Pokal for the third consecutive campaign, while also reaching the knockout stages of Europe's elite competition for the fourth time in five seasons. Another win on Wednesday would clearly take them much closer towards securing the latter aim, as it could move them five points clear of the other two teams in Group G with only nine points to play for.
Red Star, meanwhile, are competing in the Champions League group stage for the first time since the 2019-20 season, when they finished bottom of their group with only three points from six matches.
Despite dominating the Serbian SuperLiga in recent years by lifting the title on six successive occasions, Red Star had fallen at the playoff stages in the ensuing three seasons, but they were granted automatic qualification to the group stage this time around.
Like their forthcoming opponents, Barak Bakhar's side threatened upsetting Man City in their opening match when Osman Bukari provided them with a half-time lead at the Etihad Stadium, but the holders rallied after the break to win 3-1.
Red Star went on to almost fall to a fatal home defeat to Young Boys, but Bukari was the hero once again as his 88th minute strike salvaged a point for his side. That result kept their hopes of reaching the knockout stages - or dropping down to the Europa League by finishing third - alive ahead of their trip to Germany in midweek.
RB Leipzig Champions League form:
W
L
RB Leipzig form (all competitions):
W
W
D
L
D
W
Red Star Belgrade Champions League form:
L
D
Red Star Belgrade form (all competitions):
L
W
L
W
L
D
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Team News
Leipzig will remain without Willi Orban and El Chadaille Bitshiabu due to serious knee injuries, but otherwise they appear to have a fully-fit squad at their disposal.
Rose could hand Peter Gulasci a start to provide the Hungary goalkeeper with some match fitness following his long layoff due to a knee injury, while Benjamin Sesko, Dani Olmo and Timo Werner are all in the frame to start after only being named on the bench for their side's victory against Darmstadt.
Red Star, meanwhile, are sweating on the fitness of their star forward Bukari, who has scored two goals in two games in the Champions League this season. The 24-year-old has missed his side's last two matches with a knock.
Filippo Falco is still sidelined with a long-term injury, but Peter Olayinka could start in the visitors' attack, particularly if Bukari is out as expected.
RB Leipzig possible starting lineup:
Gulasci; Klostermann, Simakan, Lukeba, Lenz; Schlager, Kampl; Forsberg, Olmo; Sesko, Werner
Red Star Belgrade possible starting lineup:
Glazer; Mijailovic, Djiga, Dragovic, Rodic; Stameric, Hwang; Olayinka, Ivanic, Mitrovic; Ndiaye
We say: RB Leipzig 3-1 Red Star Belgrade
Leipzig will know the importance of collecting all three points in this match, as it would likely put them in an incredibly strong position to progress from Group G.
Red Star will be no pushovers, though, having shown plenty of resolve in their first two matches. While we can see them threatening the hosts on occasions, Rose's side should have too much quality in the end.